Visualizing mitochondrial FoF1-ATP synthase as the target of the immunomodulatory drug Bz-423

Targeting the mitochondrial enzyme FoF1-ATP synthase and modulating its catalytic activities with small molecules is a promising new approach for treatment of autoimmune diseases. The immuno-modulatory compound Bz-423 is such a drug that binds to subunit OSCP of the mitochondrial FoF1-ATP synthase and induces apoptosis via increased reactive oxygen production in coupled, actively respiring mitochondria. Here we review the experimental progress to reveal the binding of Bz-423 to the mitochondrial target and discuss how subunit rotation of FoF1-ATP synthase is affected by Bz-423. Briefly, we report how F\"orster resonance energy transfer (FRET) can be employed to colocalize the enzyme and the fluorescently tagged Bz-423 within the mitochondria of living cells with nanometer resolution.Comment: 10 pages, 2 figure

RNA Folding Pathways

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143692/1/cpnc1100.pd

Going forward

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55863/1/20632_ftp.pd

Adolescent friendship quality and emotional adjustment: examining the role of mothers' own friendships

Title from PDF of title page (University of Missouri--Columbia, viewed on May 23, 2012).The entire thesis text is included in the research.pdf file; the official abstract appears on the short.pdf file; a non-technical public abstract appears in the public.pdf.Thesis advisor: Dr. Amanda J. RoseIncludes bibliographical references."July 2011"The present study examines associations between youths' friendships and the friendships their mothers have with other adults. It was hypothesized that youth whose mothers have friendships high in positive qualities would have more positive friendships themselves and report decreased internalizing symptoms. Similarly, children of mothers whose friendships were high in negative qualities were expected to report increased negative qualities in their own friendships as well as increased internalizing symptoms. A sample of 172 fifth, eighth, and eleventh gradeyouth and their mothers were recruited to test these hypotheses, however, only the latter hypothesis was supported. Although mothers who reported high levels of conflict in their own friendships had children whose friendships were characterized by increased conflict, similar associations did not emerge for positive qualities. Further, youth whose mothers reported higher levels of negative qualities in their friendships were more likely to report increased internalizing symptoms themselves, even after reports of the mother-child relationship, youths' friendship quality, and mothers' own internalizing symptoms were controlled

Engineering Disulfide Cross‐Links in RNA Via Air Oxidation

This unit presents protocols for the synthesis of alkylthiol‐modified ribonucleosides, their incorporation into synthetic RNA, and the formation of intramolecular disulfide bonds in RNA by air oxidation. The disulfide bonds can be formed in quantitative yields between thiols positioned in close proximity by virtue of either the secondary or tertiary structure of the RNA. Disulfide cross‐links are useful tools to probe solution structures of RNA, to monitor dynamic motion, to stabilize folded RNAs, and to study the process of tertiary structure folding.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143806/1/cpnc0504.pd

36 degree step size of proton-driven c-ring rotation in FoF1-ATP synthase

Synthesis of the biological "energy currency molecule" adenosine triphosphate ATP is accomplished by FoF1-ATP synthase. In the plasma membrane of Escherichia coli, proton-driven rotation of a ring of 10 c subunits in the Fo motor powers catalysis in the F1 motor. While F1 uses 120 degree stepping, Fo models predict a step-by-step rotation of c subunits 36 degree at a time, which is here demonstrated by single-molecule fluorescence resonance energy transfer.Comment: 8 pages, 1 figur

Chemical sequencing of disulfide-crosslinked oligodeoxyribonucleotides

Oligodeoxyribonucleotides containing a novel disulfide crosslink are shown to be amenable to chemical sequencing using standard sequencing reagents following reduction of the disulfide with DTT and selective alkylation of the free thiols with N-ethylmaleimide. This strategy will facilitate conformational and molecular recognition studies of DNA stabilized by crosslinking.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30570/1/0000205.pd

Incorporation of alkylthiol chains at C-5 of deoxyuridine

A series of alkylthiol-tether homologs at C-5 of 2'-deoxyuridine have been synthesized and incorporated into DNA oligomers through solid-phase DNA phosphoramidite synthesis. DNA-ligand disulfide crosslinks have been initially addressed through formation of an n-butyl-DNA disulfide conjugate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30630/1/0000271.pd